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1.
Arch Osteoporos ; 16(1): 119, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342724

RESUMO

In this study, we assess the association between the occurrence of new fractures and vitamin D deficiency in Japanese patients with rheumatoid arthritis using our large IORRA cohort. The results suggest that vitamin D deficiency is a significant risk factor for new fractures in Japanese female patients over the age of 50 years with rheumatoid arthritis. PURPOSE: Both rheumatoid arthritis (RA) and menopause are known risk factors for the onset of osteoporosis. The occurrence of new clinical fractures in patients with RA can significantly lower quality of life. The purpose of this study was to investigate whether vitamin D deficiency in Japanese women with RA could be a risk factor for new fractures. METHODS: Between 2011 and 2017, a total of 2567 female patients with RA over the age of 50 years (mean age, 65.9 years) were enrolled in a prospective observational study. Self-reported occurrences of new fractures were verified using patient medical records. Vitamin D deficiency was defined as serum 25(OH)D levels < 20 ng/mL. Cox proportional hazards models were used to analyze the independent contributions of various risk factors to the occurrence of a new fracture. RESULTS: New clinical fractures were sustained by 205 patients in the included cases. Among them, new osteoporotic fractures were sustained by 139 patients (63 vertebral fractures and 76 non-vertebral fractures). Among all patients, the mean (SD) serum 25(OH)D level was 16.9 (5.89) ng/mL and the prevalence of vitamin D deficiency was 72.6%. A Cox proportional hazards model revealed that vitamin D deficiency was significantly associated with all new clinical fractures (hazard ratio, 1.44 [95% confidence interval 1.02‒2.05]; p = 0.0365) and all new osteoporotic fractures (hazard ratio, 1.75 [95% confidence interval 1.14‒2.69]; p = 0.0109). CONCLUSION: Vitamin D deficiency is a risk factor for new fractures in Japanese female patients over the age of 50 years with RA. Screening these patients for serum 25(OH)D could potentially be seminal to reducing their risk of fractures.


Assuntos
Artrite Reumatoide , Fraturas por Osteoporose , Deficiência de Vitamina D , Idoso , Artrite Reumatoide/epidemiologia , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Pós-Menopausa , Qualidade de Vida , Fatores de Risco , Vitamina D , Deficiência de Vitamina D/epidemiologia
2.
PLoS Comput Biol ; 17(6): e1008398, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34133418

RESUMO

Blood flow governs transport of oxygen and nutrients into tissues. Hypoxic tissues secrete VEGFs to promote angiogenesis during development and in tissue homeostasis. In contrast, tumors enhance pathologic angiogenesis during growth and metastasis, suggesting suppression of tumor angiogenesis could limit tumor growth. In line with these observations, various factors have been identified to control vessel formation in the last decades. However, their impacts on the vascular transport properties of oxygen remain elusive. Here, we take a computational approach to examine the effects of vascular branching on blood flow in the growing vasculature. First of all, we reconstruct a 3D vascular model from the 2D confocal images of the growing vasculature at postnatal day 5 (P5) mouse retina, then simulate blood flow in the vasculatures, which are obtained from the gene targeting mouse models causing hypo- or hyper-branching vascular formation. Interestingly, hyper-branching morphology attenuates effective blood flow at the angiogenic front, likely promoting tissue hypoxia. In contrast, vascular hypo-branching enhances blood supply at the angiogenic front of the growing vasculature. Oxygen supply by newly formed blood vessels improves local hypoxia and decreases VEGF expression at the angiogenic front during angiogenesis. Consistent with the simulation results indicating improved blood flow in the hypo-branching vasculature, VEGF expression around the angiogenic front is reduced in those mouse retinas. Conversely, VEGF expression is enhanced in the angiogenic front of hyper-branching vasculature. Our results indicate the importance of detailed flow analysis in evaluating the vascular transport properties of branching morphology of the blood vessels.


Assuntos
Neovascularização Patológica , Vasos Retinianos/fisiopatologia , Animais , Camundongos , Camundongos Transgênicos , Vasos Retinianos/anatomia & histologia , Vasos Retinianos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
4.
Angiogenesis ; 24(1): 159-176, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33052495

RESUMO

Receptor endocytosis is crucial for integrating extracellular stimuli of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), into the cell via signal transduction. VEGF not only triggers various angiogenic events including endothelial cell (EC) migration, but also induces the expression of negative regulators of angiogenesis, including vasohibin-1 (VASH1). While we have previously reported that VASH1 inhibits angiogenesis in vitro and in vivo, its mode of action on EC behavior remains elusive. Recently VASH1 was shown to have tubulin carboxypeptidase (TCP) activity, mediating the post-translational modification of microtubules (MTs) by detyrosination of α-tubulin within cells. However, the role of VASH1 TCP activity in angiogenesis has not yet been clarified. Here, we showed that VASH1 detyrosinated α-tubulin in ECs and suppressed in vitro and in vivo angiogenesis. In cultured ECs, VASH1 impaired endocytosis and trafficking of VEGF receptor 2 (VEGFR2), which resulted in the decreased signal transduction and EC migration. These effects of VASH1 could be restored by tubulin tyrosine ligase (TTL) in ECs, suggesting that detyrosination of α-tubulin negatively regulates angiogenesis. Furthermore, we found that detyrosinated tubulin-rich MTs were not adequate as trafficking rails for VEGFR2 endocytosis. Consistent with these results, inhibition of TCP activity of VASH1 led to the inhibition of VASH1-mediated suppression of VEGF-induced signals, EC migration, and in vivo angiogenesis. Our results indicate a novel mechanism of VASH1-mediated inhibition of pro-angiogenic factor receptor trafficking via modification of MTs.

5.
Asian Spine J ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33059436

RESUMO

Study Design: Retrospective cohort study. Purpose: This study aimed to evaluate aggravated lateral recess stenosis and clarify the indirect decompression threshold by combined lateral interbody fusion and percutaneous pedicle screw fixation (LIF/PPS). Overview of Literature: No previous reports have described an effective radiographic indicator for determining the surgical indication for LIF/PPS. Methods: A retrospective review of 185 consecutive patients, who underwent 1- or 2-level lumbar fusion surgery for degenerative spondylolisthesis (DS). According to their symptomatic improvement, they were placed into either the "recovery" or "no-recovery" group. Preoperative computed tomography (CT) images were evaluated for the position of the superior articular processes at the slipping level, followed by a graded classification (grades 0-3) using the impingement line (I line), a new radiographic indicator. All 432 superior articular facets in 216 slipped levels were classified, and both groups' characteristics were compared. Results: There were 171 patients (92.4%) in the recovery group and 14 patients in the no-recovery group (7.6%). All patients in the no-recovery group were diagnosed with symptoms associated with deteriorated bony lateral recess stenosis. All superior articular processes of the lower vertebral body in affected levels reached and exceeded the I line (I line-; grade 2 and 3) on preoperative sagittal CT images. In the recovery group, most superior articular processes did not reach the I line (I line+; grade 0 and 1; p=0.0233). Conclusions: In DS cases that are classified as grade 2 or greater, the risk of aggravated bony lateral recess stenosis due to corrective surgery is high; therefore, indirect decompression by LIF/PPS is, in principle, contraindicated.

6.
Osteoporos Sarcopenia ; 6(2): 82-87, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32715099

RESUMO

Objectives: This study aimed to evaluate factors associated with osteoporosis medication use in Japanese patients with rheumatoid arthritis (RA). Methods: Patients with RA who enrolled in our cohort completed self-administered questionnaires which included questions regarding their osteoporosis medications. Logistic regression was used to determine the association of variables with the use of these medications. Results: Among 5660 Japanese patients with RA who responded to the questionnaires (mean age, 61.8 years; 86.0% female), 1983 patients (35.0%) and 1211 patients (21.4%) reported taking osteoporosis medications and antiresorptive agents, respectively. In multivariate models, age, female sex, lower body mass index (BMI), self-reported fracture history, Japanese Health Assessment Questionnaire-Disability Index (JHAQ-DI), daily dosage of prednisone (PSL), weekly dosage of methotrexate (MTX), and concomitant use of hypertension and hyperlipidemia medications were significantly associated with the use of osteoporosis medications (P < 0.05). Among women with RA, the use of hypertension medications was significantly correlated with the use of both osteoporosis medications and antiresorptive agents (P < 0.05). Conclusions: Age, female sex, a lower BMI, duration of RA, self-reported fracture history, JHAQ-DI, daily dosage of PSL, weekly dosage of MTX, and the use of medications for hypertension and hyperlipidemia appear to be associated with the use of osteoporosis medications in Japanese patients with RA.

7.
BMC Mol Cell Biol ; 21(1): 30, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32303178

RESUMO

BACKGROUND: Transmembrane and immunoglobulin domain-containing protein 1 (TMIGD1) is a recently identified cell adhesion molecule which is predominantly expressed by epithelial cells of the intestine and the kidney. Its expression is downregulated in both colon and renal cancer suggesting a tumor suppressive activity. The function of TMIGD1 at the cellular level is largely unclear. Published work suggests a protective role of TMIGD1 during oxidative stress in kidney epithelial cells, but the underlying molecular mechanisms are unknown. RESULTS: In this study, we address the subcellular localization of TMIGD1 in renal epithelial cells and identify a cytoplasmic scaffold protein as interaction partner of TMIGD1. We find that TMIGD1 localizes to different compartments in renal epithelial cells and that this localization is regulated by cell confluency. Whereas it localizes to mitochondria in subconfluent cells it is localized at cell-cell contacts in confluent cells. We find that cell-cell contact localization is regulated by N-glycosylation and that both the extracellular and the cytoplasmic domain contribute to this localization. We identify Synaptojanin 2-binding protein (SYNJ2BP), a PDZ domain-containing cytoplasmic protein, which localizes to both mitochondria and the plasma membrane, as interaction partner of TMIGD1. The interaction of TMIGD1 and SYNJ2BP is mediated by the PDZ domain of SYNJ2BP and the C-terminal PDZ domain-binding motif of TMIGD1. We also find that SYNJ2BP can actively recruit TMIGD1 to mitochondria providing a potential mechanism for the localization of TMIGD1 at mitochondria. CONCLUSIONS: This study describes TMIGD1 as an adhesion receptor that can localize to both mitochondria and cell-cell junctions in renal epithelial cells. It identifies SYNJ2BP as an interaction partner of TMIGD1 providing a potential mechanism underlying the localization of TMIGD1 at mitochondria. The study thus lays the basis for a better understanding of the molecular function of TMIGD1 during oxidative stress regulation.


Assuntos
Células Epiteliais/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Adesão Celular/genética , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Citoplasma/metabolismo , Glicosilação , Humanos , Moléculas de Adesão Juncional/genética , Moléculas de Adesão Juncional/metabolismo , Glicoproteínas de Membrana/genética , Proteínas de Membrana/genética , Mitocôndrias/genética , Domínios PDZ/genética , Ligação Proteica
8.
Nat Commun ; 11(1): 1343, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32165640

RESUMO

Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results in hearing loss. Here we identify EPHA2 as another causative gene of Pendred syndrome with SLC26A4. EphA2 forms a protein complex with pendrin controlling pendrin localization, which is disrupted in some pathogenic forms of pendrin. Moreover, point mutations leading to amino acid substitution in the EPHA2 gene are identified from patients bearing mono-allelic mutation of SLC26A4. Ephrin-B2 binds to EphA2 triggering internalization with pendrin inducing EphA2 autophosphorylation weakly. The identified EphA2 mutants attenuate ephrin-B2- but not ephrin-A1-induced EphA2 internalization with pendrin. Our results uncover an unexpected role of the Eph/ephrin system in epithelial function.


Assuntos
Efrina-A2/genética , Bócio Nodular/genética , Perda Auditiva Neurossensorial/genética , Transportadores de Sulfato/genética , Sequência de Aminoácidos , Animais , Efrina-A1/genética , Efrina-A1/metabolismo , Efrina-A2/química , Efrina-A2/metabolismo , Efrina-B2/genética , Efrina-B2/metabolismo , Bócio Nodular/metabolismo , Perda Auditiva Neurossensorial/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação Puntual , Ligação Proteica , Transportadores de Sulfato/química , Transportadores de Sulfato/metabolismo
9.
Int J Surg Case Rep ; 68: 96-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126355

RESUMO

INTRODUCTION: A volar dislocation of the metacarpophalangeal (MCP) joint of the thumb is a rare trauma, and in combination with a radial collateral ligament (RCL) injury is much rarer. We present a surgical case with a recurrent volar dislocation of the MCP joint of the thumb with RCL injury. PRESENTATION OF CASE: A 47-year-old man was referred to our hospital in the subacute phase. Open reduction was performed through a dorsal incision and the RCL was repaired. X-rays taken six weeks later revealed a recurrent dislocation of the MCP joint. At the revision surgery, the extensor pollicis brevis (EPB) was detached from the proximal phalanx. As there was volar tightness, the volar plate was incised horizontally and the EPB was attached to the proximal phalanx. The final X-rays six months post-operatively revealed that the MCP joint was slightly subluxated but there was no pain on motion. DISCUSSION: This case revealed that it is not enough only to repair the RCL to reduce a volar dislocation of the MCP joint of the thumb with an RCL injury. It revealed that re-attachment of the extensor tendons and the volar procedure are also important for a perfect reduction of a recurrent volar dislocation of the MCP joint of the thumb. CONCLUSION: For a volar dislocation of the MCP joint of the thumb with RCL injury, it is important not only to repair the RCL, but also to perform arthroplasty with the extensor tendons and a volar procedure to prevent recurrent dislocation after surgery.

10.
J Rheumatol ; 47(4): 502-509, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31203226

RESUMO

OBJECTIVE: To investigate whether abatacept (ABA) causes more adverse events (AE) than conventional synthetic disease-modifying antirheumatic drugs (csDMARD) after orthopedic surgery in patients with rheumatoid arthritis (RA). METHODS: A retrospective multicenter nested case-control study was performed in 18 institutions. Patients receiving ABA (ABA group) were matched individually with patients receiving csDMARD and/or steroids (control group). Postoperative AE included surgical site infection, delayed wound healing, deep vein thrombosis or pulmonary embolism, flare, and death. The incidence rates of the AE in both groups were compared with the Mantel-Haenszel test. Risk factors for AE were analyzed by logistic regression model. RESULTS: A total of 3358 cases were collected. After inclusion and exclusion, 2651 patients were selected for matching, and 194 patients in 97 pairs were chosen for subsequent comparative analyses between the ABA and control groups. No between-group differences were detected in the incidence rates of each AE or in the incidence rates of total AE (control vs ABA: 15.5% vs 20.7% in total, 5.2% vs 3.1% in death). CONCLUSION: Compared with csDMARD and/or steroids without ABA, adding ABA to the treatment does not appear to increase the incidence rates of postoperative AE in patients with RA undergoing orthopedic surgery. Large cohort studies should be performed to add evidence for the perioperative safety profile of ABA.

11.
Cancer Sci ; 110(5): 1780-1789, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30801864

RESUMO

The expression of immune checkpoint proteins such as programmed cell death protein 1 (PD-1) and its ligand (PD-L1) has been shown to correlate with patient prognosis in many malignant cancers. The expression of PD-L1 is controlled by c-Myc; however, further upstream regulation of PD-L1 expression is largely unknown. We have previously shown that atypical protein kinase C lambda/iota (aPKCλ) phosphorylates the Forkhead box protein O1 (FoxO1) transcription factor at Ser218 to suppress its DNA-binding ability, thereby regulating c-Myc expression and controlling physiologic and pathologic endothelial proliferation. The presence of phosphorylation of FoxO1 at Ser218 (pSer218 FoxO1) in cutaneous angiosarcoma (CAS) strongly correlates with poor patient prognosis. Here, we reported that patients with PD-L1+ cells in CAS lesions showed significantly worse prognosis compared to those that were PD-L1- . Expression of PD-L1 correlated with that of aPKCλ or the presence of pSer218FoxO1. Moreover, suppression of aPKCλ expression or inhibition of its activity in HUVECs or AS-M, an established human angiosarcoma cell line, resulted in decreased PD-L1 expression. Our results suggest that combined treatment with immune checkpoint inhibitors and aPKCλ inhibitors could be a novel treatment strategy for CAS patients.


Assuntos
Antígeno B7-H1/metabolismo , Proteína Forkhead Box O1/metabolismo , Hemangiossarcoma/metabolismo , Isoenzimas/metabolismo , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias Cutâneas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Feminino , Proteína Forkhead Box O1/química , Regulação Neoplásica da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Fosforilação , Prognóstico , Serina/metabolismo
12.
Foot Ankle Surg ; 25(3): 348-353, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30321979

RESUMO

BACKGROUND: Recurrence of hallux valgus (HV) is a common complication after forefoot surgery for rheumatoid forefoot deformities. The aim of this study is to evaluate the impact of hindfoot malalignment on recurrence. METHODS: This was a retrospective observational study designed to analyze the radiographic outcomes of 87 feet in 64 patients with rheumatoid arthritis treated with a joint-preserving surgery for HV deformity. Differences in hindfoot alignment preoperatively between the recurrence and nonrecurrence groups was compared. RESULTS: There were no significant differences in hindfoot alignment preoperatively between groups. To estimate the impact of technical problems, the HV and intermetatarsal angles measured from radiographs 3 months postoperatively were compared between groups. The HV angles in the recurrence group were significantly larger than those in the nonrecurrence group (p=0.02). CONCLUSIONS: There were no significant differences between preoperative hindfoot malalignment and postoperative recurrence of HV in rheumatoid forefoot surgeries.


Assuntos
Artrite Reumatoide/cirurgia , Antepé Humano/cirurgia , Hallux Valgus/diagnóstico por imagem , Calcanhar/anormalidades , Complicações Pós-Operatórias/diagnóstico por imagem , Adulto , Idoso , Artrite Reumatoide/fisiopatologia , Feminino , Antepé Humano/diagnóstico por imagem , Antepé Humano/fisiopatologia , Hallux Valgus/cirurgia , Calcanhar/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Radiografia , Recidiva , Estudos Retrospectivos
13.
Mod Rheumatol ; 29(3): 430-435, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29799293

RESUMO

OBJECTIVE: The aim of this study was to investigate factors that predict a decrease in serum 25(OH)D among Japanese patients with rheumatoid arthritis (RA). METHODS: In 2011 and 2013, serum 25(OH)D was evaluated in the same 2534 Japanese patients with RA (2179 women and 355 men) who participated in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort study. A vitamin D deficiency was defined as serum 25(OH)D levels <20 ng/mL. Predictive factors resulting in decreased serum 25(OH)D over a 2-year period were evaluated using multivariate logistic regression. RESULTS: The prevalence of vitamin D deficiency was 73.3% in 2011 and 68.2% in 2013. Serum 25(OH)D levels decreased by >5 ng/mL from 2011 to 2013 in 224 (8.8%) patients. A serum 25(OH)D decrease of >5 ng/mL was significantly associated with female gender, younger age, and disuse of bisphosphonates among all patients, and younger age, higher Japanese health assessment questionnaire disability index (JHAQ-DI), increased tender joint counts, and disuse of bisphosphonates and/or active vitamin D3 among women with RA. CONCLUSION: Female gender, younger age, JHAQ-DI, tender joint counts, and disuse of bisphosphonates and/or active vitamin D3 appear to be associated with a decrease in serum 25(OH)D in Japanese patients with RA.


Assuntos
Artrite Reumatoide/complicações , Deficiência de Vitamina D/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Vitamina D/sangue
14.
Nat Commun ; 9(1): 5357, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30559384

RESUMO

Strict regulation of proliferation is vital for development, whereas unregulated cell proliferation is a fundamental characteristic of cancer. The polarity protein atypical protein kinase C lambda/iota (aPKCλ) is associated with cell proliferation through unknown mechanisms. In endothelial cells, suppression of aPKCλ impairs proliferation despite hyperactivated mitogenic signaling. Here we show that aPKCλ phosphorylates the DNA binding domain of forkhead box O1 (FoxO1) transcription factor, a gatekeeper of endothelial growth. Although mitogenic signaling excludes FoxO1 from the nucleus, consequently increasing c-Myc abundance and proliferation, aPKCλ controls c-Myc expression via FoxO1/miR-34c signaling without affecting its localization. We find this pathway is strongly activated in the malignant vascular sarcoma, angiosarcoma, and aPKC inhibition reduces c-Myc expression and proliferation of angiosarcoma cells. Moreover, FoxO1 phosphorylation at Ser218 and aPKC expression correlates with poor patient prognosis. Our findings may provide a potential therapeutic strategy for treatment of malignant cancers, like angiosarcoma.


Assuntos
Proliferação de Células/fisiologia , Células Endoteliais/metabolismo , Proteína Forkhead Box O1/metabolismo , Hemangiossarcoma/patologia , Isoenzimas/metabolismo , Proteína Quinase C/metabolismo , Animais , Linhagem Celular , Proteínas de Ligação a DNA/metabolismo , Proteína Forkhead Box O1/genética , Regulação da Expressão Gênica , Células HEK293 , Hemangiossarcoma/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Isoenzimas/genética , Camundongos , Camundongos Knockout , MicroRNAs/genética , Fosforilação , Proteína Quinase C/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética
15.
EMBO Rep ; 19(9)2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30018153

RESUMO

Impaired cell polarity is a hallmark of diseased tissue. In the cardiovascular system, laminar blood flow induces endothelial planar cell polarity, represented by elongated cell shape and asymmetric distribution of intracellular organelles along the axis of blood flow. Disrupted endothelial planar polarity is considered to be pro-inflammatory, suggesting that the establishment of endothelial polarity elicits an anti-inflammatory response. However, a causative relationship between polarity and inflammatory responses has not been firmly established. Here, we find that a cell polarity protein, PAR-3, is an essential gatekeeper of GSK3ß activity in response to laminar blood flow. We show that flow-induced spatial distribution of PAR-3/aPKCλ and aPKCλ/GSK3ß complexes controls local GSK3ß activity and thereby regulates endothelial planar polarity. The spatial information for GSK3ß activation is essential for flow-dependent polarity to the flow axis, but is not necessary for flow-induced anti-inflammatory response. Our results shed light on a novel relationship between endothelial polarity and vascular homeostasis highlighting avenues for novel therapeutic strategies.


Assuntos
Moléculas de Adesão Celular/fisiologia , Proteínas de Ciclo Celular/fisiologia , Polaridade Celular/fisiologia , Endotélio Vascular/metabolismo , Inflamação/metabolismo , Proteínas de Membrana/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Aorta/fisiopatologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Proteínas do Citoesqueleto/metabolismo , Técnicas de Silenciamento de Genes , Células HEK293 , Homeostase/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas Nucleares/metabolismo , Proteína Quinase C/metabolismo , Fluxo Sanguíneo Regional , Proteínas Repressoras/metabolismo , Transdução de Sinais
16.
J Hand Surg Asian Pac Vol ; 23(2): 192-197, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29734890

RESUMO

BACKGROUND: We reviewed our surgical results of open synovectomy with radial head resection for rheumatoid elbow. METHODS: We reviewed the 20 patients (22 elbows) underwent open synovectomy for rheumatoid elbows retrospectively. The minimum follow-up period is over 10 years, and the average was 13 years 4 months. Surgical outcomes were evaluated using the VAS pain scale, range of motion, and radiologic outcomes including Larsen's grade and carrying angle. RESULTS: The mean VAS score was 39 (range, 10-90) at last follow-up. The only one patient underwent revision surgery. The mean flexion-extension range of elbow was -28°-112° and arc of motion was 82° before surgery. The mean flexion-extension range of elbow was -23°-114°, and arc of motion was 90° at last follow-up. Radiologic findings of nine elbows in 21 elbows worsened at last follow-up according to the Larsen-s grade. Carrying angle increased by mean 4.2°, and it increased by 10° or more in four elbows. CONCLUSIONS: Our results show that open synovectomy with radial head resection resulted in functional motion maintenance and pain control for a long time, but often resulted in an elbow valgus deformity. Our findings suggest open synovectomy can be considered as palliative treatment for painful rheumatoid elbow.


Assuntos
Artrite Reumatoide/cirurgia , Articulação do Cotovelo , Rádio (Anatomia)/cirurgia , Sinovectomia , Adulto , Idoso , Artrite Reumatoide/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Radiografia , Amplitude de Movimento Articular , Reoperação , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Mod Rheumatol ; 28(6): 976-980, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29325462

RESUMO

OBJECTIVE: Since IL-6 has been associated with activation of the coagulation cascade and upregulation of fibrinogen transcription, we retrospectively tested the hypothesis that patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) may lose more blood when undergoing total knee arthroplasty (TKA). METHODS: This study included 115 RA patients who underwent primary TKA and were preoperatively tested for fibrinogen levels. The blood volume of each patient was calculated using the Nadler formula, and estimated blood loss after TKA was calculated as the change between pre-operative and post-operative hematocrits. If salvaged blood was reinfused, the volume was measured and added to the volume of the estimated blood loss. RESULTS: We observed that patients treated with TCZ had significantly lower pre-operative fibrinogen levels than those not treated with TCZ (190.0 mg/dL versus 347.0 mg/dL, respectively; p = .00018). We also observed a statistically significant increase in mean total volume of estimated blood loss after TKA in RA patients who had been treated with TCZ compared with those not treated with TCZ (797.1 mL versus 511.4 mL, respectively; p = .0039). CONCLUSION: TCZ treatment in patients with RA may increase the risk of blood loss after TKA because of decreased fibrinogen levels.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artroplastia do Joelho/efeitos adversos , Fibrinogênio/análise , Hemorragia Pós-Operatória/epidemiologia , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Semin Cell Dev Biol ; 81: 2-12, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28739340

RESUMO

The ability of cells to polarize is an intrinsic property of almost all cells and is required for the devlopment of most multicellular organisms. To develop cell polarity, cells integrate various signals derived from intrinsic as well as extrinsic sources. In the recent years, cell-cell adhesion receptors have turned out as important regulators of cellular polarization. By interacting with conserved cell polarity proteins, they regulate the recruitment of polarity complexes to specific sites of cell-cell adhesion. By initiating intracellular signaling cascades at those sites, they trigger their specific subcellular activation. Not surprisingly, cell-cell adhesion receptors regulate diverse aspects of cell polarity, including apico-basal polarity in epithelial and endothelial cells, front-to-rear polarity in collectively migrating cells, and planar cell polarity during organ development. Here, we review the recent developments highlighting the central roles of cell-cell adhesion molecules in the development of cell polarity.


Assuntos
Moléculas de Adesão Celular/metabolismo , Polaridade Celular/fisiologia , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Animais , Adesão Celular/fisiologia , Células Endoteliais/metabolismo , Humanos , Ligação Proteica
19.
Asian J Anesthesiol ; 55(4): 83-86, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29248589

RESUMO

OBJECTIVE: The aim of this study was to review and evaluate the selection and dose of anesthetic agents and the interval from the block procedure to skin incision for supraclavicular brachial plexus block in upper extremity surgery. METHODS: We reviewed our cases that underwent upper extremity surgery using only ultrasound-guided supraclavicular brachial plexus block in our hospital between 2011 and 2016. Adverse events during surgery were evaluated. Receiver operating characteristic (ROC) curves were constructed to investigate the relationship between the time from the end of the block procedure to skin incision and the use of local anesthesia on the surgical site. RESULTS: There were 255 patients who were divided into three groups according to the anesthetic agents used: group 1, 1% lidocaine (L) 10 ml + 0.75% ropivacaine (R) 20 ml (n = 62); group 2, L 20 ml + R 10 ml (n = 93); and group 3, L 10 ml + R 15 ml (n = 100). The rate of use of local anesthesia on the surgical site was significantly higher in group 3 than in the other two groups. There were no significant differences in the other evaluated items among the three groups. ROC curve analysis indicated that ≥24 min from the end of the block procedure to skin incision might reduce the use of local anesthesia. CONCLUSION: The total volume of anesthetic agents had an important influence on the rate of the addition of local anesthesia for surgical pain; however, the combined dose of agents did not influence the evaluation items. For effective analgesia, ≥24 min should elapse from the end of the block procedure to skin incision.


Assuntos
Anestésicos Locais/administração & dosagem , Bloqueio do Plexo Braquial/métodos , Ultrassonografia de Intervenção , Extremidade Superior/cirurgia , Adulto , Idoso , Anestésicos Locais/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC
20.
Nat Commun ; 8(1): 1574, 2017 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-29146905

RESUMO

Pericytes adhere to the abluminal surface of endothelial tubules and are required for the formation of stable vascular networks. Defective endothelial cell-pericyte interactions are frequently observed in diseases characterized by compromised vascular integrity such as diabetic retinopathy. Many functional properties of pericytes and their exact role in the regulation of angiogenic blood vessel growth remain elusive. Here we show that pericytes promote endothelial sprouting in the postnatal retinal vasculature. Using genetic and pharmacological approaches, we show that the expression of vascular endothelial growth factor receptor 1 (VEGFR1) by pericytes spatially restricts VEGF signalling. Angiogenic defects caused by pericyte depletion are phenocopied by intraocular injection of VEGF-A or pericyte-specific inactivation of the murine gene encoding VEGFR1. Our findings establish that pericytes promote endothelial sprouting, which results in the loss of side branches and the enlargement of vessels when pericyte function is impaired or lost.


Assuntos
Células Endoteliais/metabolismo , Olho/irrigação sanguínea , Neovascularização Fisiológica/fisiologia , Pericitos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Capilares/citologia , Capilares/crescimento & desenvolvimento , Linhagem Celular , Toxina Diftérica/toxicidade , Células Endoteliais/citologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pericitos/citologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Retina/metabolismo , Transdução de Sinais , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética
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